Protein and Peptide Nanocluster Synthesis and Functionality in Vaccine Applications
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Tsoras, Alexandra N.
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Abstract
Synthesis of protein and peptide nanoclusters (PNC) are demonstrated via desolvation for several applications and as a platform to better understand immune cell processing of subunit antigen vaccines. Nanoclusters made of protein fragments of surface antigens from bacteria that cause typhus were shown to enable antibody binding, indicating vaccine potential. Small peptides 7-14 amino acids long were synthesized into PNC for the first time. In vitro cell processing was evaluated for one PNC from a peptide epitope of a cancer antigen as a potential cancer vaccine. It was proposed that a combination of peptide modification and optimization of synthesis of PNC is needed to enable biomaterial stability and maintain desired immune cell interactions for maximal efficacy as a vaccine. Various PNC formulations with modified peptide and crosslinking stabilization methods during desolvation were evaluated in vivo for effects on antigen-specificity and immune response. Modified peptides in PNC maintained antigen-specific responses and formulation of PNC affected immune response. A dataset of peptides formed into PNC and desolvation synthesis attempts for each peptide used was compiled, and data visualization was utilized to provide a guide for future synthesis attempts with new peptides. This work demonstrates utility of PNC as a versatile platform for subunit vaccines with small peptides, proteins, and combinations of these, enabling rational design for tuned antibody and cellular immune responses in vaccine applications.
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2020-05-15
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Dissertation